Sustained-release formulation of levodopa methyl ester/benserazide for prolonged suppressing dyskinesia expression in 6-OHDA-leisoned rats
Abstract
Although levodopa remains the most effective drug in the treatment of Parkinson's disease (PD), chronic administration of levodopa in the treatment of PD usually caused levodopa-induced dyskinesia (LID), the pathogenesis of which is poorly understood. It has been demonstrated that continuous dopamine stimulation reduces the expression of LID in PD. In the present study, levodopa methyl ester (LDME) and benserazide were microencapsulated into poly (lactide-co-glycolide) (PLGA) microspheres and then administrated to PD model of rats, which were induced by 6-hydroxydopamine injections. We found that both LDME/benserazide-loaded microspheres achieved sustained-release without burst release during the first day. LDME and benserazide had the same release slope from the second day on in vivo though benserazide released faster than LDME during the whole process. In our pharmacodynamic study, LDME/benserazide-loaded microspheres decreased apomorphine-induced turns and improved stepping of the lesioned forepaw in PD rats. Moreover, western blot analysis showed that the levels of ΔfosB, phosphorylated dopamine, cAMP-regulated phosphoprotein of 32kDa at threonine 34 and extracellular signal-regulated kinases 1 and 2 were decreased by LDME/benserazide-loaded microspheres in PD rats. These data showed that LDME/benserazide-loaded microspheres could be used to treat PD motor symptoms and ameliorate the expression of LID in this rat model of PD.
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Levodopa/benserazide encapsulated in PLGA-NPs significantly reduced dyskinesis and improved PD symptoms and associated biochemical markers in PD animal model.
“Similarly, a significant reduction in dyskinesis and improvement in PD symptoms and associated biochemical markers (ΔfosB, c-AMP-regulated phosphoprotein or phosphorylated dopamine) were observed in the PD animal model after the administration of levodopa/benserazide encapsulated in PLGA-NPs.120,121”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [120]
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- Authors
- Ren, T., Yang, X., Wu, N., Cai, Y., Liu, Z., & Yuan, W.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Liu, Zhenguo
- Yuan, Weien
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 502
- Issue
- 2
- Pages
- 117-122
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2079115644
- Cited by
- 32
- References
- 29
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 3 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 4 · 2012: 1
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Shanghai Committee of Science and Technology (0952nm03700, 1052nm03900)
- Key Foundational Program of the Shanghai Committee of Science and Technology (09JC1411000)
- Key Science Development Program of Shanghai Municipal Education Commission (10ZZ72)
- Programs Foundation of Ministry of Education (20090073120085)
- Shanghai Baiyulan Talent Plan Project (1009B097)
- University Student Renovation Project of Shanghai JiaoTong University (IPP2090)
- National comprehensive technology platforms for innovative drug R&D (2009ZX09301–007)
- National Natural Science Foundation of China (81071025)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- benserazide, levodopa-induced dyskinesia, Parkinson's disease, sustained drug release, PLGA microspheres, microencapsulation, 6-hydroxydopamine lesion, ΔFosB, ERK1/2 phosphorylation, dopamine signaling, cAMP signaling, motor symptoms
- MeSH terms
- Animals, Antiparkinson Agents, Benserazide, Delayed-Action Preparations, Disease Models, Animal, Drug Combinations, Levodopa, Male, Reaction Time, Dopamine Agents, Oxidopamine, Rats, Wistar, Parkinsonian Disorders, Rats
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